1. Field of the Invention
The present invention relates to compositions and methods for treating, preventing and/or ameliorating cancers, the onset of cancers or the symptoms associated with cancers such as breast cancer, colon cancer, skin cancer, lung cancer, throat cancer, esophageal cancer, gastric cancer, pancreatic cancer, prostate cancer, bladder cancer, etc.
More particularly, the present invention relates to compositions and methods for treating, preventing and/or ameliorating cancers, the onset of cancers or the symptoms associated with cancers such as breast cancer, colon cancer, skin cancer, lung cancer, throat cancer, esophageal cancer, gastric cancer, pancreatic cancer, prostate cancer, bladder cancer, etc., where the compositions comprises a nonsteroidal anti-inflammatory drug (an NSAID) and a phospholipid where the phospholipid enhances the anti-cancer efficacy of the NSAID and the methods include administering the composition to a human or animal before or after cancer identification and where the method of administration can be oral, topical, intravenous, intra-arterial or directly into a tissue site.
2. Description of the Related Art
Cancer is the disease responsible for the majority of deaths in both the U.S. and worldwide. Although the advent of new chemotherapeutic regimens has increased patient survival once cancer is diagnosed, it has not reduced the overall incidence or severity of the disease.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested for chemoprevention of breast; colon, and other cancers based on epidemiological studies showing an inverse association between use of NSAIDs and cancer risk (1, 2). There is supporting preclinical and clinical data to suggest that NSAIDs may offer a chemopreventive strategy that is effective and inexpensive. The main limiting side effect to the use of NSAIDs is their tendency to cause gastrointestinal (GI) bleeding and lesions in susceptible patients.
NSAIDs are currently subdivided into two classes: 1) the conventional drugs like aspirin, ibuprofen (Advil or Motrin), or naproxen (Aleve), which inhibit both the constitutive cyclooxygenase-1 (COX-1) and inducible cyclooxygenase-2 (COX-2) enzyme isoforms, respectively, that serve as the rate-limiting enzymes in the conversion of arachidonic acid to prostaglandins, and 2) the recently developed and commercialized selective COX-2 inhibitors like celecoxib (Celebrex) and rofecoxib (Vioxx) (3).
The mechanism by which COX inhibition may affect cancer is under investigation and probably involves multiple factors. High expression of COX-2 results in elevated prostaglandin formation, molecules which stimulate cell proliferation (4-5). COX-2 and prostaglandins are also implicated in the induction of angiogenesis by production of factors such as vascular endothelial growth factor (6). Therefore, NSAID inhibition of these proliferative properties of prostaglandins would clearly promote anti-tumor activity. In addition, NSAIDs have recently been shown to possess COX-independent anti-cancer activity, through the induction of NSAID activated gene (NAG-1), a proapoptotic and antitumorigenic factor (7-10). NSAIDs also may affect cancer growth through inhibition of NFκB activation (11-12), by inducing the pro-apoptotic BAX gene and inhibiting the anti-apoptotic Bcl-XT protein (13), and by inducing apoptosis through activation of protein kinase G and c-Jun kinase (14).
Although the administration of conventional or COX-2 selective NSAIDs in chemoprevention of cancer has great promise, the chronic consumption of these drugs is not without risk and/or problems. The major concern with the chronic usage of these drugs is that 30-40% of consumers have a GI intolerance to NSAIDs, and suffer from a spectrum of symptoms, ranging from dyspepsia to peptic ulcer disease, which may be associated with life-threatening episodes of hemorrhage (15). One clinical study demonstrated that 30% of chronic NSAID users had at least one gastroduodenal ulcer at endoscopy (15-16). Furthermore, a retrospective study restricted to rheumatoid arthritis patients in the U.S. concluded that GI complications due to NSAID usage is responsible for 400,000 hospitalizations and 16,000 deaths annually in this patient population alone (15). It also should be noted that NSAIDs do not have to be administered at high anti-arthritic doses to induce serious GI side-effects, with evidence suggesting that the population with the greatest number of NSAID-associated GI complications requiring hospitalizations, constitute the millions of people taking low-dose aspirin for prevention of cardiovascular disease and/or cancer (17-18).
Thus, there is a need in the art for new prophylactic compositions for the prevention of the onset of cancerous growth, for the treatment of identified cancerous growths and/or for the amelioration of the symptoms associated with cancerous growth, tumor or not.